Although all cells regulate their volume and their intracellular composition of ions, the extracellular environment of the inner ear is likely to present hair cells and associated supporting cells with unique problems for ion homeostasis. Auditory transduction, which modulates the flow of ions through hair cells, places additional demands on ion homeostasis by these cells. Conversely, the intracellular ion composition of hair cells is critical to their signal processing functions. Thus the homeostatic and signal processing properties of hair cells are inextricably linked. Our overall goal is to understand ion homeostasis in the auditory sensory epithelium and its interaction with transmission of auditory signals in the cochlea. The link between homeostasis and signal processing may have important pathophysiological implications. Altered intracellular ionic composition may lead to changes, both reversible and irreversible, in cells. Thus they may play critical roles in either short- or long-term hearing losses observed in many conditions such as Meniere's Disease, overstimulation, or ototoxicity. Ion homeostasis and its relation to stimulus-induced activity can be examined in the relatively simple ear of the alligator lizard, in which many important variables can be strictly controlled. The sensory epithelium of the ear will be placed in a chamber in which the extracellular fluid composition can be regulated, controlled stimuli delivered, and the organ examined microscopically. Ion-sensitive fluorescent dyes will be used to determine intracellular sodium, calcium, and hydrogen ions in hair cells and supporting cells, at rest and during stimulation. Specific ion-transport processes that are likely to be important in regulating intracellular ionic conditions will also be examined, by observing the effects of activating or inhibiting individual ion-entry and ion-export pathways. These studies will be performed in a fluid environment similar to that in the intact animal, with different fluids bathing the endolymphatic and perilymphatic sides of the sensory epithelium. In combination with other studies on isolated hair cells, these studies will help us to determine which ion-homeostasis processes depend on the organization of hair cells and supporting cells into an epithelium.